保元解毒汤改善Apcmin/+恶病质模型肌肉萎缩的机制分析

目的:研究保元解毒汤对Apc~(min/+)恶病质小鼠血清中白细胞介素-6(IL-6)含量及腓肠肌中肌肉萎缩盒F蛋白1(Atrogin-1),肌肉特异性环指蛋白-1(MuRF-1),线粒体解偶联蛋白-2(UCP-2),解偶联蛋白-3(UCP-3)表达的影响,探讨其改善恶病质模型小鼠肌肉萎缩的作用机制。方法:14周龄Apc~(min/+)恶病质小鼠模型,随机分为模型组,保元解毒汤组(23 g·kg-1),甲地孕酮组(0. 024 g·kg-1),C57BL/6J小鼠为正常组,每组10只,连续灌胃给药12周,测定腓肠肌质量及肌纤维横径,酶联免疫吸附测定(ELISA)检测Apc~(min/+)恶病质小鼠血清中IL-6含量;蛋白免疫印迹法(Western blot),实时荧光定量聚合酶链式反应(Real-time PCR)检测小鼠腓肠肌中Atrogin-1,MuRF-1,UCP-2,UCP-3蛋白及mRNA表达。结果:与正常组比较,模型组小鼠腓肠肌质量、纤维横径明显减小(P 0. 05),血清IL-6含量显著升高,小鼠腓肠肌中Atrogin-1,MuRF-1,UCP-2,UCP-3 mRNA及蛋白表达明显升高(P 0. 05);与模型组比较,给药组小鼠腓肠肌质量、腓肠肌纤维横径显著增加,血清中IL-6含量明显降低,腓肠肌中Atrogin-1,MuRF-1,UCP-2,UCP-3 mRNA及蛋白表达明显降低(P 0. 05)。结论:保元解毒汤可改善Apc~(min/+)恶病质小鼠模型肌肉萎缩,其机制可能与降低血清中IL-6含量,下调Atrogin-1,MuRF-1表达,降低线体体UCP-2,UCP-3 mRNA表达相关。

Mechanism of Baoyuan Jiedu Decoction in Alleviating Muscle Atrophy in Apcmin/+ Cachexia Mice

Objective: To study the effect of Baoyuan Jiedu decoction on serum interleukin-6 (IL-6) content, expression of muscle atrophy F-box 1(Atrogin-1), muscle ring finger-1 (MuRF-1), uncoupling proteins-2 (UCP-2), uncoupling proteins-3 (UCP-3) in Apc^min/+ mice, in order to explore the mechanism in improving muscle atrophy in cancer cachexia model. Method: The 14-week-old Apc^min/+ cachexia mice model was randomly divided into model group, Baoyuan Jiedu decoction group (23 g·kg^-1) and megestrol group (0.024 g·kg^-1). C57BL/6J mice were normal group, with 10 mice in each group, and given continuous intragastric administration for 12 weeks. The quality of gastrocnemius muscle and the transverse diameter of muscle fibers were measured. The content of IL-6 in serum of Apc^min/+ cachexia mice was detected by enzyme-linked immunosorbent assay (ELISA). The expressions of Atrogin-1, MuRF-1, UCP-2, UCP-3 mRNA and protein in gastrocnemius muscle were detected by Western blot and quantitative real-time fluorescence polymerase chain reaction (Real-time PCR). Result: Compared with the normal group, the weight of gastrocnemius muscle and the transverse diameter of fibers in the model group decreased significantly (P<0.05), while the concentration of IL-6 in serum and the expressions of Atrogin-1, MuRF-1, UCP-2 and UCP-3 in gastrocnemius muscle of mice increased significantly (P<0.05). Compared with the model group, the weight of gastrocnemius muscle, the expression of UCP-3 and protein in the treated group increased significantly (P<0.05). The transverse diameter of muscle fibers increased significantly, whereas the concentration of IL-6 in serum and the expressions of Atrogin-1, MuRF-1, UCP-2 and UCP-3 in gastrocnemius muscle of mice decreased significantly (P<0.05). Conclusion: Reduction of the concentration of IL-6 in serum and the down-regulation of the expressions of Atrogin-1, MuRF-1, UCP-2 and UCP-3 genes may be the possible mechanism of Baoyuan Jiedu decoction in alleviating muscle atrophy in Apc^min/+ cachexia mice model.